Water → 2-[2-(4-Fluoro-2,3-dihydro-3,3-dimethyl-1H-indol-1-yl)-2-oxoethyl]-6-(4-morpholinyl)-4(3H)-pyrimidinone

HRID 2278569Notes

Reaction equation

HRID 2278569 reaction equation
[F:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[C:4]([CH3:12])([CH3:11])[CH2:5][NH:6]2.Cl.CN(C)CCCN=C=NCC.[N:25]1([C:31]2[N:32]=[C:33]([CH2:38][C:39]([O-])=[O:40])[NH:34][C:35](=[O:37])[CH:36]=2)[CH2:30][CH2:29][O:28][CH2:27][CH2:26]1.[Na+].O>CN(C)C=O.N1C=CC=CC=1>[F:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[C:4]([CH3:12])([CH3:11])[CH2:5][N:6]2[C:39](=[O:40])[CH2:38][C:33]1[NH:34][C:35](=[O:37])[CH:36]=[C:31]([N:25]2[CH2:26][CH2:27][O:28][CH2:29][CH2:30]2)[N:32]=1

Participants

7

Reactant 4

HCID 962WaterHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 72698802HCID 72698802, compoundHCID 136041844Sodium (4-morpholin-4-yl-6-oxo-1,6-dihydropyrimidin-2-yl)acetate

Product 1

HCID 1361388332-[2-(4-Fluoro-2,3-dihydro-3,3-dimethyl-1H-indol-1-yl)-2-oxoethyl]-6-(4-morpholinyl)-4(3H)-pyrimidinoneYield 55.3%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6228DimethylformamideSolvent

Procedure

150 mg of 4-fluoro-3,3-dimethyl-2,3-dihydro-1H-indole [reference example 2c] and 279 mg of N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride are added to a solution of 261 mg of sodium [1-methyl-4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetate (obtained in step 2c of example 1c) in 5 ml of N,N-dimethylformamide and 5 ml of pyridine. The reaction mixture is stirred at ambient temperature for 16 hours and then 30 ml of water are added and the mixture is extracted with ethyl acetate. The organic phase is washed successively with water and a saturated sodium chloride solution, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue is purified by trituration from a mixture of ethyl acetate and diisopropyl ether, so as to give 194 mg of 2-[2-(4-fluoro-3,3-dimethyl-2,3-dihydro-1H-indol-1-yl)-2-oxoethyl]-6-(morpholin-4-yl)pyrimidin-4(3H)-one, the characteristics of which are the following:

Workup

  1. extractionthe mixture is extracted with ethyl acetate
  2. washThe organic phase is washed successively with water
  3. dry with materiala saturated sodium chloride solution, dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue is purified by trituration from a mixture of ethyl acetate and diisopropyl ether

Sources & evidence

ORD record
ord-c848d3aed7c146e7803c7412a95f287b
Source dataset
uspto-grants-2015_09
Patent number
US09133168B2

Reaction notes

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